缺血性脑血管病的现代研究进展

脑卒中是一种常见的脑血管疾病,其中绝大多数脑卒中病例是由短暂性或永久性脑血管闭塞引起的缺血性脑血管病(缺血性中风),具有分辨率高、致残率高、死亡率高的特点。目前,在临床实践中已经研究出许多策略用于改善缺血性中风的脑部抢救和恢复,包括抗氧化策略、神经元保护策略、抗炎策略等。进一步探究缺血性中风的病理机制及寻找有效的药物,是目前亟需解决的问题。该文简要总结近年来对于缺血性脑血管病的最新研究进展,为未来临床治疗及研究提供思路。     

血栓烷A2——新型抗缺血性脑卒中药物治疗靶点

血栓烷A2（TXA2）是血小板聚集和释放的强诱导剂,促进血栓形成;TXA2也可以引起动脉血管收缩,调节血管张力。近年来,越来越多的研究证实了TXA2诱导缺血性脑卒中发生和促进其进展的作用。这提示,TXA2可成为新型抗缺血性脑卒中药物治疗靶点。本文主要探讨了TXA2参与缺血性脑卒中发生与发展的机制,并对以TXA2为靶点防治缺血性脑卒中的药物进行综述。     

JAK/STAT信号转导通路及中药干预在缺血性脑卒中的研究进展

缺血性脑卒中是老年人常见疾病,该疾病的高发病率、高死亡率以及高致残率特点使其成为全球关注的健康难题。JAK/STAT途径作为一条新近发现的信号转导通路,广泛参与神经元生长、分化、凋亡等过程,并且与脑卒中的病理生理过程密切相关,但目前对该通道在缺血性脑卒中疾病中的功能和作用机制尚未能完全阐明。该文将结合国内外JAK/STAT通路与缺血性脑卒中疾病的最新研究报道,对JAK/STAT信号转导途径在缺血脑卒中疾病过程中的作用和机制进行综述,并系统绘制缺血性脑卒中神经病变过程各种相关信号分子的网络关系图,以便更深入了解脑卒中病理发生过程,为寻找抗脑缺血疾病治疗新药,提供较为系统的科学文献支持。     

蛋白激酶C在脑缺血再灌注损伤中的作用

缺血性脑卒中以其高发病率、高致残率和高死亡率严重危害着人类健康.缺血性脑损伤的病理生理机制极为复杂,其涉及到许多相关基因和蛋白(如:凋亡易感基因、Bcl-2蛋白家族、谷胱甘肽过氧化物酶及热休克蛋白等)的表达变化.目前FDA认证的治疗缺血性脑卒中的药物仅有重组组织型纤溶酶原激活剂(Recombinant tissue plasminogen activator,rtPA)一种.其主要原因是缺血性脑损伤是由如炎症、自由基等多种因素导致的,而多数药物仅作用于个别或少数靶点,且副作用明显,导致治疗结果不佳,因此对新型药物的研究和开发成了治疗缺血性脑卒中的重点.研究发现蛋白激酶C(Protein kinase C,PKC)可能参与调节脑缺血再灌注损伤,并有望成为治疗缺血性脑卒中的新靶点.本文就PKC及各个亚型在缺血再灌注损伤中的作用作一系统综述.     

心理康复治疗对脑卒中偏瘫患者焦虑抑郁情绪的影响

<正>脑卒中是一种高致残性致死疾病,严重影响患者健康。脑卒中是由于脑部血管突然破裂或因血管阻塞导致血液不能流入大脑,而引起脑组织损伤的疾病,主要分为出血性脑卒中和缺血性脑卒中,具体表现为短暂性或永久性脑功能障碍,丧失部分生活能力和劳动力,给家庭造成严重的经济负担~([1])。临床中对脑卒中的治疗多以降脂药物、抗凝药物、降压药物等为主,只能够有效控制患者病情,难以达到理想的治疗效果。相关的研究指出,对脑卒中偏瘫患者实施心理康复治疗有助于提升康复效果,达到提高患者生活质量的目的~([2])。本院选取70例     

阿托伐他汀与拜阿司匹林联合治疗方案对缺血性脑卒中患者颈动脉斑块以及疾病复发率的影响

<正>缺血性脑卒中是临床脑血管疾病的主要类型,且具有高病死率、高病残率以及高复发率的临床特点。目前他汀类药物的调脂作用、阿司匹林的抗血小板凝集作用已经被临床广泛的认可,成为治疗缺血性脑卒中的常规药物。而作为新生代的阿托伐他汀,其在缺血性脑卒中患者作用机制还有待更深层次的探讨。本组研究将阿托伐他汀与拜阿司匹林运用于缺血性脑卒中患者的治疗,探     

缺血性脑卒中的炎症及抗炎药物的研究进展

缺血性脑卒中(IS)是指由于脑的供血动脉(颈动脉和椎动脉)狭窄或闭塞、脑供血不足导致的脑组织坏死的总称。其为发达国家三大死亡原因之一。近年来,炎症在缺血性脑卒中中的作用引起广泛关注,小胶质细胞及众多炎性因子参与了炎症反应,根据IS炎症反应的机制可采取具有抗炎作用的药物治疗。本文就缺血性脑卒中的炎症反应机制及抗炎药物的研究进展进行综述。     

急性缺血性脑卒中溶栓治疗的研究进展

脑卒中是我国成年人致死、致残的重要病因之一,具有发病率高、复发率高、致残和死亡率高的特点。目前早期溶栓治疗是被广泛认可且积极有效的主要治疗方式。而溶栓药物重组组织纤溶酶原激活剂(rt-PA)是FDA批准的唯一缺血性脑卒中药物,但在临床使用中有诸多限制。近年来临床上关于溶栓治疗的研究发展迅速,本文将对急性缺血性脑卒中(acute ischemic stroke,AIS)的溶栓治疗进行归纳和总结,以期为AIS药物治疗提供思路。     

载脂蛋白B/载脂蛋白A1比值对缺血性脑血管病风险的预测

<正>缺血性脑血管病是指在供应脑的血管壁病变或血流动力学障碍的基础上发生的脑部血液供应障碍,导致相应供血区脑组织缺血、缺氧而出现脑组织坏死或软化,并引起短暂或持久的局部或弥漫性损害,造成一系列神经功能缺损症候群。缺血性脑血管病是导致人类死亡的三大主要疾病之一,具有高发病率、高致残率、高病死率的特点。缺血性脑血管病的发病基础是动脉粥样硬化,而高脂血症可加速动脉粥样硬化的发生,与缺血性脑卒中的发生有关。     

Apollo支架在症状性大脑中动脉狭窄介入治疗中的临床应用

<正>颅内大动脉和颈内动脉狭窄是缺血性脑卒中的常见原因,在我国高达33%的脑卒中是由颅内动脉病变引起的。症状性大脑中动脉(middle cerebral artery,MCA)狭窄是缺血性脑卒中高危人群,其预后较差。长期以来抗血小板、调脂等内科疗法一直被认为是治疗缺血性脑卒中有效的治疗方法,但对严重颅内动脉狭窄,即使予以正规的药物治疗,脑梗死的发生率和病死率仍然很高。     

胆固醇/高密度脂蛋白-胆固醇比值在脑梗死中的价值研究

目的:探讨胆固醇/高密度脂蛋白-胆固醇比值(TC/HDL-C比值)与脑梗死发病危险性的关系以及这一比值在脑梗死患者合并高血压或糖尿病时的变化。方法:选择197例脑梗死患者分为三组:单纯脑梗死组、合并高血压组、合并糖尿病组。58例健康者作为正常对照组,探讨这一比值的变化。结果:胆固醇(TC)水平及TC/HDL-C比值在脑梗死患者与正常对照组间有显著性差异(P<0.05);脑梗死患者的HDL-C水平较正常对照组降低,但两者差异无显著性(P>0.05);不同病例组间TC、HDL-C水平及TC/HDL-C比值无显著性差异(P>0.05)。结论:TC/HDL-C比值是脑梗死的危险因素,与高血压、糖尿病无关。     

Glycoprotein IIb/IIIa antagonists in acute ischaemic stroke: current status and future directions

Glycoprotein (GP) IIb/IIIa receptors on the surface of platelets play a critical role in thrombosis. Intravenous GP IIb/IIIa antagonists abciximab, tirofiban and eptifibatide have demonstrated efficacy in acute coronary syndromes when combined with heparin, aspirin, clopidogrel and percutanous coronary interventions. Results have been less consistent in acute ischaemic stroke. Preclinical data support the potential benefit of these agents both in the microcirculation and in aiding clot lysis. While phase I and II trials of abciximab as the sole agent employing dosages comparable with those used in coronary syndromes were promising, the pivotal phase III trial was abandoned because of an unfavourable benefit-to-risk ratio. New preliminary platelet inhibition measurements from our group suggest that cardiac dosages were likely to be too high for stroke patients. Exploration of lower dosages of abciximab and potentiation with time-limited weight-based heparin along with platelet aggregation inhibition measurement is continuing on a smaller scale. At present, the most common usage of GP IIb/IIIa antagonists in stroke are as adjunctive agents to thrombolysis by intravenous and intra-arterial routes. Substantial progress is likely to require a better understanding of the mechanism of actions and unique pharmacology of GP IIb/IIIa antagonists in ischaemic stroke.     

The relationship between cholesterol and stroke: implications for antihyperlipidaemic therapy in older patients

Various studies on the relationship between serum cholesterol level and the risk of stroke have been published recently. Subsequent reviews have extrapolated information on stroke from the clinical trials originally aimed at lowering cholesterol for the primary and secondary prevention of myocardial infarction (MI) in middle-aged patients. We have reviewed the epidemiological knowledge on the relationship between serum cholesterol levels and stroke, and also focused on possible reduction of the risk of stroke with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor treatment. Possible benefits from such therapy are particularly relevant for the elderly population which is at particularly high risk for stroke. The effects of serum cholesterol levels on the risk for haemorrhagic and ischaemic stroke have been evaluated. Indirect epidemiological evidence indicates that serum levels of total cholesterol and its subfractions are determinants of stroke, but their associations are relatively weak. When exploring the possible association of serum cholesterol levels with the increased risk of stroke with aging, we concluded that, as in younger adults, elevated total cholesterol and decreased high density lipoprotein-cholesterol levels predispose to ischaemic stroke in the elderly. The mechanism through which serum cholesterol levels increase stroke risk is based on its actions on the artery walls. Indirect evidence suggests that the reduction in the stroke risk with HMG-CoA reductase inhibitors is larger than would be expected with reduction of elevated serum cholesterol level alone. Therefore, antioxidant and endothelium-stabilising properties of HMG-CoA reductase inhibitors may contribute in reducing the risk of stroke in recipients. Lowering high serum cholesterol with HMG-CoA reductase inhibitors has been beneficial in the primary and secondary prevention of MI. No trials have specifically tested the effect of cholesterol lowering with HMG-CoA reductase inhibitors on stroke occurrence. High serum cholesterol levels are a risk factor for ischaemic stroke, although the risk imparted is lower than that for MI. Although the relative risk of stroke associated with elevated serum cholesterol levels is only moderate, its population attributable risk is high given the increase in the elderly population worldwide. The effect of cholesterol reduction with HMG-CoA reductase inhibitors on prevention of ischaemic stroke should be evaluated in prospective, randomised, placebo-controlled trials in the elderly. The tolerability of lipid-lowering drugs in the elderly and the cost effectiveness of primary prevention of stroke using lipid-lowering drugs also needs to be assessed in the elderly.     

进展性缺血性卒中的危险因素研究进展

进展性缺血性卒中是常见的卒中类型,发病率约占卒中的 30％,具有高致残率、高死亡率、高经济负担的特点。在临床工作中,因对疾病的危险因素了解不全面,常出现诊治不足,因此,熟知疾病的危险因素具有十分重要的意义。该文着眼于当前临床上进展性卒中的可控危险因素,如血压因素、代谢因素、血氧含量、体温和感染等;探讨了进展性缺血性卒中危险因素的研究进展,同时也关注危险因素对血管内溶栓病人的影响,为临床工作提供帮助。     

Medical prevention of stroke and stroke recurrence in patients with TIA and minor stroke

Background: Secondary stroke prevention after transient ischemic stroke (TIA) or minor stroke is of major importance in order to avoid recurrent cerebrovascular events and decrease morbidity and mortality. Objective/methods: Systematically review of recently published, high-quality studies emphasizing the need for emergency assessment and treatment of patients with TIA and minor stroke and to give a comprehensive and distinct overview over medical secondary stroke prevention trials performed in these patients. Results/conclusions: Evaluation and implementation of preventive stroke therapy has to be immediate in patients with TIA and stroke. For patients with non-cardioembolic stroke, antiplatelet agents are the treatment of choice. Aspirin plus extended-release dipyridamole and clopidogrel are more effective than aspirin and should be used in patients with a high risk of recurrent stroke. Oral anticoagulation is highly effective in patients with a cardiac source of embolism. Treatment of risk factors such as arterial hypertension and high cholesterol is even more important in secondary stroke prevention than in primary prevention. Vitamin supplementation and lowering of elevated levels of homocysteine are not effective in stroke prevention.     

Burden of stroke in the Kingdom of Saudi Arabia: A soaring epidemic

Stroke is a key cerebrovascular disease that is related to high morbidity and mortality in the globe. The Kingdom of Saudi Arabia (KSA) is not an exception where stroke is fast developing into a serious challenge due to the high mortality rate. Additionally, stroke presents a tremendous economic burden and has a devastating effect on the quality of lives of individuals. The number of stroke cases are increasing yearly, thus posing a major challenge to the health care system. Therefore, it is crucial to implement primary and secondary prevention strategies in the KSA. Nevertheless, as compared with developed countries, information on the prevalence, socio-demographic properties and prevention of stroke remains scarce that could be attributed to the shortage of research conducted in this specified region. The review is written to address the various aspects of stroke in the KSA, based on current literatures search using PubMed, Scopus, Web of Science and Google Scholar databases, to identify studies published since inception to Dec 2020.     

丁基苯酞对脑卒中型自发性高血压大鼠寿命及卒中后神经症状的影响

本实验研究了dl-3-正丁基苯酞(NBP)在高盐负荷下,对卒中型自发性高血压大鼠(SHRsp)寿命及卒中后存活时间和神经症状的影响。实验证明NBP能延迟脑卒中发生;能延长脑卒中发作后的存活时间和减轻神经症状。NBP对SHRsp大鼠的血压和心率无明显影响。     

MLN-519. Millennium/PAION

Millennium Pharmaceuticals Inc (formerly LeukoSite Inc) and PAION GmbH are developing MLN-519, a ubiquitin/proteasome enzyme inhibitor, for the potential treatment of inflammatory diseases and stroke. MLN-519 is currently undergoing phase I clinical trials in acute stroke and myocardial infarction, and is poised to enter phase II trials.     

Excess salt intake promotes M1 microglia polarization via a p38/MAPK/AR-dependent pathway after cerebral ischemia in mice

A high salt diet (HSD) is among the most important risk factors for many diseases. One mechanism by which HSD aggravates cerebral ischemic injury is independent of blood pressure changes. The direct role of HSD in inflammation after cerebral ischemia is unclear. In this research, after twenty-one days of being fed a high salt diet, permanent focal ischemia was induced in mice via operation. At 12 h and 1, 3 and 5 days postischemia, the effects of HSD on the lesion volume, microglia polarization, aldose reductase (AR) expression, and inflammatory processes were analyzed. We report that in mice, surplus dietary salt promotes inflammation and increases the activation of classical lipopolysaccharide (LPS)-induced microglia/macrophages (M1). This effect depends on the expression of the AR protein in activated microglia after permanent middle cerebral artery ligation (pMCAL) in HSD mice. The administration of either the AR inhibitor Epalrestat or a p38-neutralizing antibody blocked the polarization of microglia and alleviated stroke injury.In conclusion, HSD promotes polarization in pro-inflammatory M1 microglia by upregulating the expression of the AR protein via p38/MAPK, thereby exacerbating the development of ischemia stroke.     

Primary and secondary stroke prevention with antiplatelet drugs

Aspirin is not effective in the primary prevention of stroke. Patients with TIA or ischemic stroke carry a risk of recurrent stroke between 5 and 20% per year. In patients with TIA or ischemic stroke of noncardiac origin antiplatelet drugs are able to decrease the risk of stroke by 11-15% and the risk of stroke, MI and vascular death by 15-22%. Aspirin is the most widely used drug. It is affordable and effective. Low doses of 50-325 mg aspirin are as effective as high doses and cause less gastrointestinal side effects. Severe bleeding complications are dose-dependent. The combination of aspirin with slow release dipyridamole is superior to aspirin alone for stroke prevention. Clopidgrel is superior to aspirin in patients at high risk of recurrence. The combination of aspirin plus clopidogrel is not more effective than clopidogrel alone but carries a higher bleeding risk. None of the antiplatelet agents is able to reduce mortality.